Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification.

BACKGROUND: Inflammatory arthritis (IA) is an immune-related condition defined by the presence of clinical synovitis. Its most common form is rheumatoid arthritis. OBJECTIVE: To develop scores for predicting IA in at-risk persons using multidimensional biomarkers. DESIGN: Prospective observational cohort study. SETTING: Single-center, Leeds, United Kingdom. PARTICIPANTS: Persons with new musculoskeletal symptoms, a positive test result for anticitrullinated protein antibodies, and no clinical synovitis and followed for 48 weeks or more or until IA occurred. MEASUREMENTS: A simple score was developed using logistic regression, and a comprehensive score was developed using the least absolute shrinkage and selection operator Cox proportional hazards regression. Internal validation with bootstrapping was estimated, and a decision curve analysis was done. RESULTS: Of 455 participants, 32.5% (148 of 455) developed IA, and 15.4% (70 of 455) developed it within 1 year. The simple score identified 249 low-risk participants with a false negative rate of 5% (and 206 high-risk participants with a false-positive rate of 72%). The comprehensive score identified 119 high-risk participants with a false-positive rate of 29% (and 336 low-risk participants with a false-negative rate of 19%); 40% of high-risk participants developed IA within 1 year and 71% within 5 years. LIMITATIONS: External validation is required. Recruitment occurred over 13 years, with lower rates of IA in later years. There was geographic variation in laboratory testing and recruitment availability. CONCLUSION: The simple score identified persons at low risk for IA who were less likely to need secondary care. The comprehensive score identified high-risk persons who could benefit from risk stratification and preventive measures. Both scores may be useful in clinical care and should also be useful in clinical trials. PRIMARY FUNDING SOURCE: National Institute for Health and Care Research Leeds Biomedical Research Centre.

Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions.

BACKGROUND: Biologic and targeted synthetic disease modifying agents (b/tsDMARDs) have broadened the treatment landscape for autoimmune diseases particularly in patients refractory to conventional DMARDs. More recently, the introduction of biosimilars has reduced the price of bDMARDs, potentially improving accessibility. Though efficacy and safety have been described, patient attitudes to b/tsDMARDs are not well-understood. We aim to investigate patients' beliefs about biologic and biosimilar therapy, and the factors influencing their perceptions. METHODS: Patient consumer groups (Arthritis Australia, Crohn's and Colitis Australia) assisted in advertising an online questionnaire for people with a self-reported diagnosis of inflammatory arthritis (IA) or inflammatory bowel disease (IBD). The questionnaire incorporated the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS). Sources and favourability of biologic/biosimilar information were analysed, using the chi-square and a non-parametric trend test for unordered and ordered categorical variables respectively, comparing respondents with IA and IBD. RESULTS: Eight hundred and thirty eight people (686-IA, 144-IBD, 8 both) responded. 658 (79%) used b/tsDMARDs. The BMQ demonstrated high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics. 95% of respondents obtained medication information from specialists though most used multiple sources (median 4). The most positive resources were specialists and specialist nurses. 73/141 (52%) respondents with IBD obtained information from specialist nurses compared with 202/685 (29%) with IA (p = 0.012). Respondents with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Younger respondents and those with higher BMQ concern scores more frequently consulted less reliable sources (e.g. social media). 502 respondents (60%) answered the biosimilar questions. Only 23 (4.6%) reported currently using a biosimilar and 336 (66.9%) were unsure if biosimilars were available in Australia. Specialist recommendation was the most frequent factor that would influence a patient to change from originator to biosimilar (352/495, 71.1%). CONCLUSIONS: There is a high level of trust in specialists' recommendations about b/tsDMARDs, although most people also utilise additional information sources. Contextual factors influencing resource selection include age, reading ability and degree of concern about medicines. People with IA and IBD have similar attitudes though those with IBD more frequently access specialist nurse advice.

Hand and foot MRI in contemporary undifferentiated arthritis: in which patients is MRI valuable to detect rheumatoid arthritis early? A large prospective study.

OBJECTIVES: Identifying patients that will develop RA among those presenting with undifferentiated arthritis (UA) remains a clinical dilemma. Although MRI is helpful according to EULAR recommendations, this has only been determined in UA patients not fulfilling 1987 RA criteria, while some of these patients are currently considered as RA because they fulfil the 2010 criteria. Therefore, we studied the predictive value of MRI for progression to RA in the current UA population, i.e. not fulfilling RA classification criteria (either 1987 or 2010 criteria) and not having an alternate diagnosis. Additionally, the value of MRI was studied in patients with a clinical diagnosis of UA, regardless of the classification criteria. METHODS: Two UA populations were studied: criteria-based UA as described above (n = 405) and expert-opinion-based UA (n = 564), i.e. UA indicated by treating rheumatologists. These patients were retrieved from a large cohort of consecutively included early arthritis patients that underwent contrast-enhanced MRI scans of hand and foot at baseline. MRIs were scored for osteitis, synovitis and tenosynovitis. Patients were followed for RA development during the course of 1 year. Test characteristics of MRI were determined separately for subgroups based on joint involvement and autoantibody status. RESULTS: Among criteria-based UA patients (n = 405), 21% developed RA. MRI-detected synovitis and MRI-detected tenosynovitis were predictive for progression to RA. MRI-detected tenosynovitis was independently associated with RA progression (odds ratio (OR) 2.79; 95% CI 1.40, 5.58), especially within ACPA-negative UA patients (OR 2.91; 95% CI 1.42, 5.96). Prior risks of RA development for UA patients with mono-, oligo- and polyarthritis were 3%, 19% and 46%, respectively. MRI results changed this risk most within the oligoarthritis subgroup: positive predictive value was 27% and negative predictive value 93%. Similar results were found in expert-opinion-based UA (n = 564). CONCLUSION: This large cohort study showed that MRI is most valuable in ACPA-negative UA patients with oligoarthritis; a negative MRI could aid in preventing overtreatment.

MRI-detected synovitis of the small joints predicts rheumatoid arthritis development in large joint undifferentiated inflammatory arthritis.

OBJECTIVES: New onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at first presentation. We assessed clinical and serological features associated with RA development in patients with an undifferentiated mono- or oligo-articular large joint arthritis, and with keen interest in whether an MRI of the small joints of the hand and foot would aid diagnosis. METHODS: Leiden Early Arthritis Clinic includes 4018 patients; this prospective study follows 221 consecutively included patients with new onset undifferentiated large joint arthritis. Baseline clinical data and serology were obtained. Forty-five patients had MRIs (hand and foot). MRIs were scored according to the OMERACT RAMRIS. Univariable and multivariable logistic regression were assessed. Test characteristics, predictive values and net reclassification index (NRI) for RA were determined. RESULTS: Patients mostly presented with knee or ankle mono-arthritis. During the 12 months' follow-up 17% developed RA. Autoantibody positivity (ACPA and/or RF) and MRI-detected synovitis in hands and feet were independently associated with RA development in multivariable analyses [odds ratio 10.29 (P = 0.014) and 7.88 (P = 0.017), respectively]. Positive predictive value of autoantibodies, MRI-detected synovitis and combination of both features was 63%, 55% and 100%, respectively. The addition of MRI-detected synovitis to autoantibody status improved diagnostic accuracy (NRI 18.1%). CONCLUSION: In patients presenting with undifferentiated large joint arthritis, 17% will develop RA. Autoantibody positivity and subclinical synovitis are independent predictors. The data suggest MRI of small joints is beneficial for early identification of RA in large joint arthritis.

Value of imaging detected joint inflammation in explaining fatigue in RA at diagnosis and during the disease course: a large MRI study.

OBJECTIVE: Fatigue in rheumatoid arthritis (RA) is hypothesised to be caused by inflammation. Still ~50% of the variance of fatigue in RA cannot be explained by the Disease Activity Score (DAS), nor by background or psychological factors. Since MRI can detect joint inflammation more sensitively than the clinical joint counts as incorporated in the DAS, we hypothesised that inflammation detected by MRI could aid in explaining fatigue in RA at diagnosis and during the follow-up. METHODS: 526 consecutive patients with RA were followed longitudinally. Fatigue was assessed yearly on a Numerical Rating Scale. Hand and foot MRIs were performed at inclusion, after 12 and 24 months in 199 patients and were scored for inflammation (synovitis, tenosynovitis and osteitis combined). We studied whether patients with RA with more MRI-inflammation were more fatigued at diagnosis (linear regression), whether the 2-year course of MRI-inflammation associated with the course of fatigue (linear mixed models) and whether decrease in MRI-inflammation in year 1 associated with subsequent improvement in fatigue in year 2 (cross-lagged models). Similar analyses were done with DAS as inflammation measure. RESULTS: At diagnosis, higher DAS scores were associated with more severe fatigue (p<0.001). However, patients with more MRI-inflammation were not more fatigued (p=0.94). During 2-year follow-up, DAS decrease associated with improvement in fatigue (p<0.001), but MRI-inflammation decrease did not (p=0.96). DAS decrease in year 1 associated with fatigue improvement in year 2 (p=0.012), as did MRI-inflammation decrease (p=0.039), with similar effect strength. CONCLUSION: Sensitive measurements of joint inflammation did not explain fatigue in RA at diagnosis and follow-up. This supports the concept that fatigue in RA is partly uncoupled from inflammation.

Tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA: a large cross-sectional MRI study.

OBJECTIVES: Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognisable at joint examination, hence its prevalence can therefore be underestimated. We hypothesised that if MRI-detectable tenosynovitis is a true RA feature, the sensitivity for RA is high, in both anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA, and lower in other diseases that are associated with enthesitis (such as spondyloarthritis (SpA) and psoriatic arthritis (PsA)). So far, no large MRI study addressed these questions. METHODS: Consecutive patients with early arthritis (n=1211) from one healthcare region underwent contrast-enhanced 1.5T MRI of hand and foot at diagnosis. MRIs were scored for synovitis and tenosynovitis by two readers blinded for clinical data. All included patients with ACPA-positive RA (n=250), ACPA-negative RA (n=282), PsA (n=88), peripheral SpA (n=24), reactive arthritis (n=30) and self-limiting undifferentiated arthritis (UA; n=76) were studied. Sensitivity was calculated. RESULTS: The sensitivity of tenosynovitis in RA was 85%; 88% for ACPA-positive RA and 82% for and ACPA-negative RA (p=0.19). The sensitivity for RA was significantly higher than for PsA (65%; p=0.001), SpA (53%; p<0.001), reactive arthritis (36%; p<0.001) and self-limiting UA (42%; p<0.001). The observed sensitivity of MRI synovitis was 91% in RA and ranged from 83% to 54% in other groups. CONCLUSIONS: MRI-detected tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA. This supports that both juxta-articular (tenosynovitis) and intra-articular synovial involvement is characteristic of RA.